plinabulin (BPI 2358) / BeyondSpring, Jiangsu Hengrui Pharma - LARVOL DELTA

Phase 2 study of pembrolizumab (pembro) plus plinabulin (plin) and docetaxel (doc) for patients (pts) with metastatic NSCLC after progression on first-line immune checkpoint inhibitor alone or combination therapy: Initial efficacy and safety results on immune re-sensitization. (ASCO 2025) - P2 | "Pembro plus plin and doc in pts with metastatic NSCLC who developed PD on ICI shows promising efficacy, with doubling PFS and DCR compared with historical data of doc. The AEs of the triple combination treatment is manageable. Further investigations into which pts would benefit from continued ICI treatment after progression is warranted."

Checkpoint inhibition • Clinical • Combination therapy • IO biomarker • Metastases • P2 data • Cardiovascular • Hypertension • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • ALK • APC • EGFR

BeyondSpring Announces Poster Presentation at 2025 ASCO Annual Meeting (The Manila Times) - "BeyondSpring Inc...today announces that it will have a poster presentation on 303 Study, the investigator-initiated study supported by Merck...and BeyondSpring in 2L/3L NSCLC who progressed on PD-1/PD-L1 inhibitors at 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, taking place on May 30 through June 3 in Chicago, IL."

P2 data • Non Small Cell Lung Cancer

PLINABULIN AND SELUMETINIB INDUCE AAMS REPROGRAMMING INTO M1-LIKE MACROPHAGES AND REDUCE AML CELL VIABILITY (EHA 2025) - "We then evaluated gene expression changes under the combination treatment of AZD6244 and revumenib (a Menin inhibitor) to assess AAM repolarization. In conclusion, we found that BPI-2358 and AZD6244 can reprogram AAMs into M1-like macrophages, enhancing their pro-inflammatory features and phagocytic capacity while reducing AAM-CD163⁺ levels and AML viability, representing a promising therapeutic approach in combination with targeted therapies in AML."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD163 • CD34 • CD80 • KIT • MN1 • MRC1 • NOS2 • TNFA

BeyondSpring Reports 2024 Year-End Financial Results and Highlights Key Clinical & Strategic Milestones (GlobeNewswire) - "Expected 2025 Milestones - Plinabulin: 1H 2025: Updated data from Phase 2 of Study 303 in metastatic NSCLC progressed on PD-1/PD-L1 inhibitors. 2H 2025: Preliminary data from Phase 2 of Study 302 in 1L ES-SCLC. SEED: Mid-2025: Expected IND filing of RBM39 degrader. 2H 2025: RBM39 degrader expected to begin patient enrollment. 2H 2025: Tau degrader expected to achieve in vivo efficacy."

IND • New trial • P2 data • Non Small Cell Lung Cancer • Small Cell Lung Cancer

Plinabulin in Combination With Radiation/Immunotherapy in Patients With Select Advanced Cancers After Progression on PD-1 or PD-L1 Targeted Antibodies (clinicaltrials.gov) - P1/2 | N=19 | Terminated | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Jun 2025 ➔ Feb 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: Jun 2025 ➔ Feb 2025; PI requested.

Trial completion date • Trial primary completion date • Trial termination • Bladder Cancer • Cutaneous Melanoma • Genito-urinary Cancer • Lung Cancer • Melanoma • Merkel Cell Carcinoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Skin Cancer • Small Cell Lung Cancer • Solid Tumor • MSI

Design, synthesis and anticancer evaluation of novel 1,3-imidazole-type phenylhistin derivatives: Dual mechanism via P53 induction and microtubulin inhibition. (PubMed, Bioorg Chem) - "Notably, 8 f displayed activity comparable to that of plinabulin, while 8 g was five times more potent. Molecular docking studies confirmed higher binding scores and stronger affinities for these derivatives at the colchicine-binding site of α, β-tubulin. These findings suggest that the apoptosis-inducing and cytotoxic activities of these derivatives may offer potential clinical value for tumor therapy."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Pembrolizumab in Combination with Plinabulin and Docetaxel for Metastatic NSCLC After ICIs (KeyPemls-004) (clinicaltrials.gov) - P2 | N=47 | Active, not recruiting | Sponsor: Peking Union Medical College Hospital | Recruiting ➔ Active, not recruiting

Enrollment closed • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • ROS1

KeyPemls-005: First Line Pembrolizumab, Plinabulin Plus Etoposide and Platinum (EP) for ES-SCLC (clinicaltrials.gov) - P2 | N=45 | Recruiting | Sponsor: Xiaorong Dong | Not yet recruiting ➔ Recruiting

Enrollment open • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Diverse microtubule-destabilizing drugs induce equivalent molecular pathway responses in endothelial cells. (PubMed, bioRxiv) - "Several MT-destabilizing drugs, including vinblastine, combretastatin A4, and plinabulin, are widely used, or are under evaluation for cancer treatment...To investigate whether differential modulation of molecular pathways might account for clinical differences, we compared gene expression and signaling pathway responses in human pulmonary microvascular endothelial cells (HPMECs), alongside the MT-stabilizing drug docetaxel and the pro-inflammatory cytokine TNF-α...This finding suggests that their distinct clinical effects are not caused by different effects on MTs, but rather by differences in drug transport, pharmacokinetics or tubulin isotype affinity. Our findings provide insights into how plinabulin might protect the bone marrow and may help medicinal chemists design MT drugs for new applications."

Journal • Chemotherapy-Induced Neutropenia • Hematological Disorders • Infectious Disease • Neutropenia • Oncology • TNFA

Plinabulin exerts an anti-proliferative effect via the PI3K/AKT/mTOR signaling pathways in glioblastoma. (PubMed, Iran J Basic Med Sci) - "Combined with the AKT/mTOR inhibitors LY294002 and rapamycin, plinabulin decreased p-mTOR and EGFR protein levels and increased cleaved-PARP levels. Additionally, plinabulin combined with erlotinib showed greater cytotoxic efficacy than either drug alone in glioblastoma cells in vitro. Our study provides new insights into the efficacy of plinabulin against glioblastoma and highlights the potential clinical utility of combining plinabulin with EGFR inhibitors as a chemotherapy strategy."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

BeyondSpring Announces $35.4 Million Sale of a Portion of Equity Interest in SEED Therapeutics to Advance Lead Asset Plinabulin to Anti-Cancer Registrational Studies (GlobeNewswire) - "BeyondSpring Inc...announced that it has entered into definitive agreements to sell a portion of its Series A-1 Preferred Shares of SEED Therapeutics Inc. ('SEED'), a biotechnology company focused on Targeted Protein Degradation (TPD) technology and a subsidiary of the Company, for gross proceeds of approximately $35.4 million. Upon completion of the transactions, BeyondSpring, together with SEED Technology Limited, a majority-owned indirect subsidiary of the Company, is expected to retain approximately 14.4% of SEED’s outstanding shares....The recent Series A-3 financing led by Eisai, at a pre-money valuation of $100 million, underscores SEED’s innovation and market potential....The $35.4 million in proceeds will advance BeyondSpring’s late-stage clinical trials of its lead asset, Plinabulin, ensuring critical resources without diluting shareholder equity."

Commercial • Non Small Cell Lung Cancer • Small Cell Lung Cancer

Osteosarcoma biomarker analysis and drug targeting prediction based on pyroptosis-related genes. (PubMed, Medicine (Baltimore)) - "Our findings suggest potential mechanisms of action for 22 pyroptosis-related genes in osteosarcoma and preliminarily predicted that the occurrence of osteosarcoma is closely related to pyroptosis, apoptosis, and immune regulation. Predicted Triethyl phosphate, Plinabulin, Siltuximab as potential osteosarcoma treatments."

Biomarker • Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • CASP3 • CASP8 • IL18 • IL1A • IL1B • IL6 • TP53

Plinabulin and Selumetinib Enhance M1 Macrophage Traits and Trigger Cell Death in AML (ASH 2024) - "Additionally, both drugs were associated with reduced mitochondrial membrane potential in leukemic blasts and AAMs, suggesting an impact on mitochondrial metabolism. In conclusion, we found that both BPI-2358 and AZD6244 exhibit potential in repolarizing M2-like TAMs towards an M1-like phenotype, and have cytotoxic activity in AAM and leukemic blasts thus representing a promising avenue for enhancing AML treatment strategies."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD14 • CD163 • CD34 • CD80 • CD86 • HOXA9 • KIT • MN1 • MRC1 • TNFA

Phase 2 study of pembrolizumab (pemb) plus plinabulin (plin) and docetaxel (doc) for NSCLC patients (pts) after failure on immune checkpoint inhibitor therapy: initial efficacy and safety results (SITC 2024) - P2 | "Conclusions With good tolerability, pemb plus plin and doc in pts with metastatic NSCLC who progressed after clinical benefit to ICI demonstrated promising efficacy with doubled ORR, doubled PFS, and tripled DCR compared with historical controls of chemotherapy. Ethics Approval This study was approved by Peking Union Medical College Hospital's Ethics Board; approval number I-22PJ575."

Checkpoint inhibition • Clinical • Late-breaking abstract • P2 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma

Plinabulin in Combination With Radiation/Immunotherapy in Patients With Select Advanced Cancers After Progression on PD-1 or PD-L1 Targeted Antibodies (clinicaltrials.gov) - P1/2 | N=19 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Recruiting ➔ Active, not recruiting | N=12 ➔ 19

Combination therapy • Enrollment change • Enrollment closed • Metastases • Bladder Cancer • Cutaneous Melanoma • Genito-urinary Cancer • Lung Cancer • Melanoma • Merkel Cell Carcinoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Skin Cancer • Small Cell Lung Cancer • Solid Tumor • MSI

BTCRC-LUN17-127: A Phase I/II Study of Nivolumab, Ipilimumab and Plinabulin in Patients With Recurrent Small Cell Lung Cancer (clinicaltrials.gov) - P1/2 | N=39 | Completed | Sponsor: Salma Sabbour | Active, not recruiting ➔ Completed

Trial completion • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

BeyondSpring Presents Updated Efficacy Results from a Phase 2 IIT Study of Triple IO Combo of Pembrolizumab plus Plinabulin/Docetaxel in Metastatic NSCLC after Progressing on Prior Immune Checkpoint Inhibitors at the 39th SITC Annual Meeting (GlobeNewswire) - P2 | N=47 | NCT05599789 | "Of the 30 treated patients (median age at 68.0 years; ranged 50-77 years), 73.3% were male and 26.7% were female; 60% were current or former smokers. Histology included 57% patients (n=17) with non-squamous cell carcinoma and 43% (n=13) with squamous cell carcinoma. The median follow-up was 11.5 months....The combination was generally well tolerated. 46.7% of patients experienced grade 3 or higher treatment-related adverse effects. Most common AE is myelosuppression (13.3%), GI side effect (13.3%), and transient hypertension (6.7%). There were no treatment-related deaths. Results are consistent with the data reported on the first 19 patients in Study 303 at ESMO in September."

P2 data • Non Small Cell Lung Cancer

Plinabulin/docetaxel versus docetaxel in survival benefits of 2L/3L EGFR wild-type NSCLC after platinum regimens (DUBLIN-3): A randomized phase III trial (ESMO 2024) - P3 | "Plinabulin is a novel immune-chemotherapeutic agent that enhances dendritic cell maturation and T cell proliferation. Plinabulin and docetaxel significantly improved OS, ORR, PFS, 2- and 3- year OS rates, and significantly decreased the incidence of Grade 4 neutropenia. Additional 2-year survival follow-up showed sustained survival benefit."

Clinical • P3 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • TIGIT

Phase II study of pembrolizumab (pemb) plus plinabulin (plin) and docetaxel (doc) for patients (pts) with metastatic NSCLC after failure on first-line immune checkpoint inhibitor alone or combination therapy: Initial efficacy and safety results on Immune Re-sensitization (ESMO 2024) - P2 | "Pemb plus plin and doc in pts with metastatic NSCLC who experienced progressive disease after clinical benefit to ICI was associated with prolonged PFS and DCR compared with historical controls of chemotherapy, with tolerable safety. Clinical trial information: NCT05599789."

Checkpoint inhibition • Clinical • Combination therapy • Metastases • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma

Plinabulin plus docetaxel versus docetaxel in patients with non-small-cell lung cancer after disease progression on platinum-based regimen (DUBLIN-3): a phase 3, international, multicentre, single-blind, parallel group, randomised controlled trial. (PubMed, Lancet Respir Med) - P3 | "Plinabulin plus docetaxel significantly improved OS as second-line and third-line treatment in patients with advanced or metastatic EGFR wild-type NSCLC and could be considered as a new treatment option in this population."

Journal • P3 data • Cardiovascular • Gastroenterology • Gastrointestinal Disorder • Hypertension • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Plinabulin, a microtubule destabilising agent, in non-small-cell lung cancer: lessons from the DUBLIN-3 trial. (PubMed, Lancet Respir Med) - No abstract available

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

BeyondSpring Presents Efficacy/Safety Results from a Phase 2 Study of Pembrolizumab plus Plinabulin/Docetaxel in Metastatic NSCLC after Progressing on First-Line Immune Checkpoint Inhibitors at ESMO Congress 2024 (GlobeNewswire) - P2 | N=47 | KeyPemls-004 (NCT05599789) | "BeyondSpring Inc...presented interim phase 2 data on the 303 Study, a study in 2L/3L non-small cell lung cancer (NSCLC) after disease progression on 1L PD-1/L1 inhibitors with and without chemotherapy, with financial support from Merck & Co., Inc’s (NYSE: MRK, known as MSD outside of the United States and Canada) Investigator Studies Program and provision of study drug, at the European Society for Medical Oncology (ESMO) Congress 2024, on September 14, 2024 in Barcelona, Spain....'Compared to historical controls of 3-4 months of median PFS2, this study’s early efficacy data doubled median PFS to 8.6 months, with an impressive disease control rate of almost 90%, which is encouraging and clinically meaningful for this severe unmet need'..."

P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

BeyondSpring Presents Final Data Analysis of DUBLIN-3 Phase 3 Study in 2L/3L EGFR Wild-type NSCLC at ESMO Congress 2024 (GlobeNewswire) - P3 | N=559 | DUBLIN-3 (NCT02504489) | Sponsor: BeyondSpring Pharmaceuticals Inc. | "BeyondSpring Inc...presented final data on Dublin-3 study (2L/3L EGFR wild-type NSCLC) focusing on safety outcomes on September 14, 2024 at European Society for Medical Oncology (ESMO) Congress 2024 in Barcelona, Spain....The combination arm had a 5.3 % Grade 4 neutropenia in Cycle 1 Day 8 compared to 27.8% in docetaxel alone (81% reduction, p<0.0001). The combination arm had a 5.1 % Grade 4 neutropenia in all cycles Day 8 compared to 33.6% in docetaxel alone (85% reduction, p<0.0001)....Post-hoc analysis showed reduced G-CSF use in the combination arm (152 [56%] patients) vs. docetaxel arm (182 [66%] patients) and at cycles 1 to 4."

P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

BeyondSpring Delivers Oral Presentation at ISLAC 2024 World Conference on Lung Cancer of its Lead Anti-Cancer Asset Plinabulin Showcasing Positive Final Phase 3 Data in 2L/3L NSCLC EGFR Wild-Type with Concurrent Publication in the Lancet Respiratory Medicine (GlobeNewswire) - P3 | N=559 | DUBLIN-3 (NCT02504489) | Sponsor: BeyondSpring Pharmaceuticals Inc. | "BeyondSpring Inc...announces Dublin-3 final phase 3 efficacy data of its late clinical-stage agent Plinabulin in combination with docetaxel in second/third line (2L/3L) advanced and metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) wild-type....Favorable benefit/risk ratio: Significant improvement in OS (Hazard ratio or HR=0.82; same HR in the Western vs. Asian patients), PFS (HR=0.79) and ORR (nearly doubled). Durable anti-cancer benefits in doubling 24-months and 36-months OS rates. And 82% relative reduction in Grade 4 neutropenia in Cycle 1 Day 8 (p<0.0001). Consistent OS benefit in 24-month follow up after the database lock: OS HR=0.81 in the ITT population, with better OS benefit in the non-squamous subset (OS HR=0.72, p=0.0078)."

P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Plinabulin/Docetaxel vs. Docetaxel in 2L/3L NSCLC after Platinum Regimens (DUBLIN-3): A Phase 3 Randomized Controlled Trial (IASLC-WCLC 2024) - P3 | "Conclusions : In patients with advance EGFR wild-type platinum refractory NSCLC, plinabulin combined with docetaxel was well-tolerated and statistically significantly improved OS/PFS/ORR with reduced severe neutropenia. A durable anti-cancer benefit was observed suggesting that plinabulin/docetaxel as a potential practice-changing treatment for advanced/metastatic NSCLC without driver mutations."

Clinical • P3 data • Cardiovascular • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hypertension • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR